Phospholipids are highly surface active species that passivate electrodes. Although they are oxidized chemically, this surface activity in conjunction with slow electrochemical kinetics has precluded their direct determination electrochemically. Described is an approach that uses a nanoscale silica sol-gel film on the electrode to address the adsorption problem and to immobilize an electron-transfer catalyst. Preliminary results showed that silica sol-gels are resistant to passivation by the phospholipid. The sol-gel film will be fabricated by an electrochemically assisted process. It limits the sol-gel reaction to the surface, resulting in non-conductive films with thicknesses in the range 10 - 200 nm. To impart conductivity, which is required for the goal of fabricating an amperometric detector, we will either template pores normal to the electrode surface or dope the film with electron-transfer mediators, such as dirhodium-substituted phosphomolybic acid, that conduct by electron self-exchange. One design for alleviating the adsorption will involve templating pore size into the regime smaller than that of the phospholipid. Here, the required catalyst is hosted by the so-gel phase. The second design will template pores into the regime greater than the size of the phospholipid. In this case, layer-by-layer assembly in the pores of a network of catalyst and conducting polymer will "wire" the film. Electrochemical reaction will occur at the head of the network. Relative merits of these approaches will be described. The pore distribution will be a variable in the study. The goal is to have sufficient dispersion to give radial-diffusion control of the current. Amperometric detection of phosphatidylcholine and cardiolipin after HPLC will be a typical test system. A detection limit of 0.01 - 0.1 picomoles in a 10 ?L injection is projected. PUBLIC HEALTH RELEVANCE: The project will result in an improved method of detection of phospholipids following their chromatographic separation. One target, cardiolipin, is an indicator of the initial step in cell apoptosis and relates to, for example, heart failure, rheumatoid arthritis, and Barth Syndrome. Success with the platforms under investigation can be extended in the biomedical field to designing selective biopsy probes and perhaps in situ measurements.